CDP-diacylglycerol (DAG) is an important branch point intermediate just downstream of phosphatidic acid (PA) in the pathways for biosynthesis of glycerophosphate-based phospholipids (Kent, Anal. Rev. Biochem. 64: 315-343, 1995). In eukaryotic cells, PA, the precursor molecule for all glycerophospholipid, is converted either to CDP-DAG by CDP-DAG synthase (CDS) or to DAG by a phosphohydrolase. In mammalian cells, CDP-DAG is the precursor to phosphatidylinositol (PI), phosphatidylglycerol (PG), and cardiolipin (CL). Diacylglycerol is the precursor to triacylglycerol, phosphatidylethanolamine, and phosphatidylcholine in eukaryotic cells. Therefore, the partitioning of phosphatidic acid between CDP-diacylglycerol and diacylglycerol must be an important regulatory point in eukaryotic phospholipid metabolism (Shen et al., J. Biol. Chem. 271:789-795, 1996). In eukaryotic cells, CDP-diacylglycerol is required in the mitochondria for phosphatidylglycerol and cardiolipin synthesis and in the endoplasmic reticulum and possibly other organelles for the synthesis of phosphatidylinositol (PI). PI, in turn, is the precursor for the synthesis of a series of lipid second messengers, such as phosphatidylinositol-4,5-bisphosphate (PIP.sub.2), DAG and inositol-1,4,5-trisphosphate (IP.sub.3). Specifically, PIP.sub.2 is the substrate for phospholipase C that is activated in response to a wide variety of extracellular stimuli, leading to the generation of two lipid second messengers; namely, DAG for the activation of protein kinase C and IP.sub.3 for the release of Ca.sup.++ from internal stores (Kent, Anal. Rev. Biochem. 64: 315-343, 1995).
The genes coding for CDS have been identified in E. coli (Icho et al, J. Biol. Chem. 260:12078-12083, 1985), in yeast (Shen et al., J. Biol. Chem. 271:789-795, 1996), and in Drosophila (Wu et al., Nature 373:216-222, 1995). The cloning of a mammalian version of CDS has not been reported. It is of interest to isolate the cDNAs coding for human CDS and express it in mammalian cells to determine the potential roles of this enzyme in cellular function and to use this enzyme as a target for the development of specific compounds that are modulators of its activity. With the advance in the understanding of disease processes, it has been found that many diseases result from the malfunction of intracellular signaling. This recognition has led to research and development of therapies based on the interception of signaling pathways in diseases (Levitzki, Curr. Opin. Cell Biol. 8:239-244, 1996). Compounds that would modulate CDS activity, and hence generation of a variety of lipid second messengers and modulate the signals involved in cell activation, may be of therapeutic interest in the areas of inflammation and oncology. This patent is based upon the cloning and expression of a human CDS cDNA.